Organic Stereochemistry. Part 2

Testa, Bernard

doi:10.1002/hlca.201200470

Cited by 23 publications

(5 citation statements)

References 65 publications

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“…Alternatively, when considering handedness, if a backbone is completely flat (say, a ring, where d = 0), handedness ( h ) will be undefined, and so one can not speak of handedness of the twist. Yet, the backbone may still remain chiral; e.g., cisplatin and transplatin are planar molecules that are nonetheless chiral opposites ( Testa, 2013 ). It is for this reason that this report chooses to be careful to not claim that Eq.…”

Section: Methodsmentioning

confidence: 99%

An exhaustive survey of regular peptide conformations using a new metric for backbone handedness (h)

Mannige

2017

PeerJ

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The Ramachandran plot is important to structural biology as it describes a peptide backbone in the context of its dominant degrees of freedom—the backbone dihedral angles φ and ψ (Ramachandran, Ramakrishnan & Sasisekharan, 1963). Since its introduction, the Ramachandran plot has been a crucial tool to characterize protein backbone features. However, the conformation or twist of a backbone as a function of φ and ψ has not been completely described for both cis and trans backbones. Additionally, little intuitive understanding is available about a peptide’s conformation simply from knowing the φ and ψ values of a peptide (e.g., is the regular peptide defined by φ = ψ = − 100° left-handed or right-handed?). This report provides a new metric for backbone handedness (h) based on interpreting a peptide backbone as a helix with axial displacement d and angular displacement θ, both of which are derived from a peptide backbone’s internal coordinates, especially dihedral angles φ, ψ and ω. In particular, h equals sin(θ)d∕|d|, with range [−1, 1] and negative (or positive) values indicating left(or right)-handedness. The metric h is used to characterize the handedness of every region of the Ramachandran plot for both cis (ω = 0°) and trans (ω = 180°) backbones, which provides the first exhaustive survey of twist handedness in Ramachandran (φ, ψ) space. These maps fill in the ‘dead space’ within the Ramachandran plot, which are regions that are not commonly accessed by structured proteins, but which may be accessible to intrinsically disordered proteins, short peptide fragments, and protein mimics such as peptoids. Finally, building on the work of (Zacharias & Knapp, 2013), this report presents a new plot based on d and θ that serves as a universal and intuitive alternative to the Ramachandran plot. The universality arises from the fact that the co-inhabitants of such a plot include every possible peptide backbone including cis and trans backbones. The intuitiveness arises from the fact that d and θ provide, at a glance, numerous aspects of the backbone including compactness, handedness, and planarity.

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Section: Methodsmentioning

confidence: 99%

An exhaustive survey of regular peptide conformations using a new metric for backbone handedness (h)

Mannige

2017

PeerJ

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“…These papers describe studies of the rate of racemisation of ar ange of compounds in aqueous media and led to as ummary of the structure-racemisation relationships for the general-base-mediated reaction. [149,150] For compounds of type R 1 R 2 R 3 CH to racemise, there should be two or three of the groups that decrease stabilityo ft he chiral centre, shown in Ta ble 10. These can be combined only with neutralg roups,t he presence of any of the groups that increases tabilityi ss ufficient to remove the risk of racemisation.I tc an be seen that the groups that decrease stability of the stereogenic centre do so by stabilising an adjacent negative chargee ither by delocalisation or by induction and those that increase stability of as tereogenic centre destabilise adjacent negative charges.…”

Section: Tools To Understand and Predict Racemisation Ratesmentioning

confidence: 99%

Racemisation in Chemistry and Biology

Ballard

Narduolo

Ahmed

et al. 2020

Chemistry A European J

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The two enantiomers of a compound often have profoundly different biological properties and thus their liability to racemisation in aqueous solutions is an important piece of information. The authors reviewed the available data concerning the process of racemisation in vivo, in the presence of biological molecules (e.g., racemase enzymes, serum albumin, cofactors and derivatives) and under purely chemical but aqueous conditions (acid, base and other aqueous systems). Mechanistic studies are described critically in light of reported kinetic data. The types of experimental measurement that can be used to effectively determine rate constants of racemisation in various conditions are discussed and the data they provide is summarised. The proposed origins of enzymatic racemisation are presented and suggest ways to promote the process that are different from processes taking place in bulk water. Experimental and computational studies that provide understanding and quantitative predictions of racemisation risk are also presented.

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“…Alternatively, when considering handedness, if a backbone is completely flat (say, a ring, where d = 0), handedness (h) will be undefined, and so one can not speak of handedness of the twist. Yet, the backbone may still remain chiral; e.g., cisplatin and transplatin are planar molecules that are nonetheless chiral opposites (Testa, 2013). It is for this reason that this report chooses to be careful to not claim that Eqn.…”

Section: Backbone Chirality = = = Backbone Handednessmentioning

confidence: 99%

Peer Review #1 of "An exhaustive survey of regular peptide conformations using a new metric for backbone handedness (h) (v0.1)"

2017

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The Ramachandran plot is important to structural biology as it describes a peptide backbone in the context of its dominant degrees of freedom-the backbone dihedral angles φ and ψ (Ramachandran et al., 1963). Since its introduction, the Ramachandran plot has been a crucial tool to characterize protein backbone features. However, the conformation or twist of a backbone as a function of φ and ψ has not been completely described for both cis and trans backbones. Additionally, little intuitive understanding is available about a peptide's conformation simply from knowing the φ and ψ values of a peptide (e.g., is the regular peptide defined by φ = ψ = −100 • left-handed or righthanded?). This report provides a new metric for backbone handedness (h) based on interpreting a peptide backbone as a helix with axial displacement d and angular displacement θ, both of which are derived from a peptide backbone's internal coordinates, especially dihedral angles φ, ψ and ω. In particular, h equals sin(θ)d/|d|, with range [−1, 1] and negative (or positive) values indicating left(or right)-handedness. The metric h is used to characterize the handedness of every region of the Ramachandran plot for both cis (ω = 0 •) and trans (ω = 180 •) backbones, which provides the first exhaustive survey of twist handedness in Ramachandran (φ , ψ) space. These maps fill in the 'dead space' within the Ramachandran plot, which are regions that are not commonly accessed by structured proteins, but which may be accessible to intrinsically disordered proteins, short peptide fragments, and protein mimics such as peptoids. Finally, building on the work of Zacharias and Knapp (2013), this report presents a new plot based on d and θ that serves as a universal and intuitive alternative to the Ramachandran plot. The universality arises from the fact that the co-inhabitants of such a plot include every possible peptide backbone including cis and trans backbones. The intuitiveness arises from the fact that d and θ provide, at a glance, numerous aspects of the backbone including compactness, handedness, and planarity.

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Organic Stereochemistry. Part 2

Cited by 23 publications

References 65 publications

An exhaustive survey of regular peptide conformations using a new metric for backbone handedness (h)

An exhaustive survey of regular peptide conformations using a new metric for backbone handedness (h)

Racemisation in Chemistry and Biology

Peer Review #1 of "An exhaustive survey of regular peptide conformations using a new metric for backbone handedness (h) (v0.1)"

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